P1296: THE LONG-TERM STRUCTURAL CHANGE OF THE GUT MICROBIOTA TRIGGERED BY ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION
Authors: Akihisa Hino, Kentaro Fukushima, Shinsuke Kusakabe, Tomoaki Ueda, Takao Sudo, Jiro Fujita, Daisuke Motooka, Takafumi Yokota, Hirohiko Shibayama, Shota Nakamura, Naoki Hosen
Journal: HemaSphere (2023)

Topic: 22. Stem cell transplantation - Clinical Background: The human intestinal flora is composed of over 40 trillion bacteria. The gut microbiota plays an essential role in sustaining human life by regulating immunity, physiological functions, and nutrition. Recent studies revealed that abnormalities in the gut microbiota have been associated with various diseases, including carcinogenesis, autoimmune diseases, and infection. After allogeneic hematopoietic stem cell transplantation (allo-HSCT), the gut microbiota shows decreased microbial diversity and domination by a single bacterium, such as Enterococcus or Streptococcus. The decreased diversity has also been associated with increased risks for acute graft-versus-host disease (aGVHD) and aGVHD-related mortality. This decreased diversity persists up to 1-year post-transplant, but how long it continues with improved lifestyles after discharge is unexplore. Aims: We examined long-term microbial changes in post-transplant survivors. The relationship between gut microbiota and post-transplant late complications was also analyzed Methods: We analyzed the gut microbiota of 59 patients who survived for 1–21.7 years (median, 6.4 years) after allo-HSCT. For comparison, fecal samples from 59 healthy controls (HC), matched for age and sex, were also analyzed. Bacterial DNA was extracted from fecal samples, and the gut microbial community was evaluated using the alpha and beta diversities with the Shannon index and weighted unique fraction distances, respectively. Subsequently, linear discriminant analysis effect size identified differentially abundant bacteria between groups with a logarithmic linear discriminant analysis score threshold of ±3.0. Results: Long-term survivors showed lower gut microbial diversity than the healthy controls. This decreased diversity was reflected in the reduced abundance of the butyrate-producing bacteria, Coprococcus and Faecalibacterium. We compared gut microbiotas in patients at <3 years, 3–10 years, and >10 years after transplantation to assess changes. The gut microbiota of long-term survivors showed no recovery of diversity over time. The abundance of Coprococcus was significantly lower in all categories than in the HC group. These results indicate that alterations in the gut microbiota persisted for >10 years after transplantation, without improvements in diversity and structure. Age and sex did not affect the alpha and beta diversities of the gut microbiota. In this study, at the time of sample collection, the patients were not hospitalized and were not under any dietary restrictions. Additionally, the use of antibiotics and probiotics did not significantly impact the reduced microbiota diversity of long-term survivors in this study. These findings suggest that hospitalization, discontinuing dietary restriction and antibiotics, and administering probiotics are insufficient to re-establish gut microbial diversity in long-term survivors. Summary/Conclusion: We observe the gut microbiota in long-term survivors for more than a year and to reveal that microbial dysbiosis does not recover over a 10-year lifetime after discharge. These changes may affect the late complications such as chronic graft-versus-host disease and secondary cancers, which can be problematic in the long post-transplant life. Furthermore, we concluded that not only a comprehensive metagenomic evaluation was needed, but also interventions to ameliorate dysbiosis early and maintain it in the long term. Keywords: Allogeneic hematopoietic stem cell transplant, Second malignancy, Graft-versus-host disease (GVHD)